Tumor‐specific immunity can be enhanced by transfection of tumor cells with syngeneic MHC‐class‐II genes or allogeneic MHC‐class‐I genes

Mouse Sal sarcoma cells are lethal in the autologous A/J ( K k D d ) host. In order to improve the immune response to the Sal tumor, Sal cells have been transfected with syngeneic MHC‐class‐II or allogeneic MHC‐class‐I genes. MHC‐class‐II transfectants are uniformly rejected by the autologous host and immunization with them protects against subsequent Sal challenge. The improved immunity is probably the result of enhanced generation of tumor‐specific T h cells. We hypothesize that class‐II + tumor cells trigger an improved T h ‐cell response because they directly present Sal tumor antigens in the context of class‐II molecules to T h cells, by‐passing professional APC. Studies by others have demonstrated that antigen presentation requires an intracellular signal transmitted by the cytoplasmic domain of the APC class‐II molecule. Sal cells expressing class‐ll antigens with truncated cytoplasmic domains are as malignant as wild‐type Sal cells. These experiments therefore support the role of tumor‐cell class‐II molecules as antigen presentation elements, and demonstrate the requirement for intact class‐II molecules for tumor protection. Sal cells have also been transfected with allogeneic MHC‐class‐I genes. Although K b ‐transfected cells are not rejected by A/J mice, D b ‐transfected Sal cells and K b ‐ plus D b ‐transfected cells are rejected. The D b transfectants effectively immunize A/J mice against subsequent Sal challenge. These experiments demonstrate that expression of certain allogeneic MHC‐class‐I genes can lead to tumor‐specific immunity, and that such transfectants can protect against challenges of wild‐type tumor cells. Transfection of tumor cells with syngeneic MHC‐class‐II or allogeneic MHC‐class‐I genes may therefore be a potential strategy for improving tumor‐specific immunity in the autologous host.